Among the various cell types involved in immune responses, T lymphocytes play the major regulatory roles. While T cells interact with other leukocytes by direct contact involving cell surface molecules, they also secrete a large variety of regulatory factors. Partially or highly purified preparations of some of these factors from various sources have been shown to mediate or regulate distinct immune responses in in vitro or in vivo experimental systems. See, for example, David, J. R. and Remold, H. G. (1976) In: Immunology of the Macrophage, Ed. D. S. Nelson (Academic Press, NY), p. 401.
When T cells are placed in culture and stimulated with polyclonal T cell mitogens, they secrete into the culture medium antigen-nonspecific factors (lymphokines) of a broad spectrum of activities associated with T cell functions. Morley, J., et al. (1978) In: Handbook of Experimental Immunology, Ed. D. M. Weis (Blackwell Scientific Publications, Oxford), Chapter 27; Rocklin, R. E. et al. (1980) Adv. Immunol. 29, 55; Oppenheim, J. J. (1981) In: Cellular Functions in Immunity and Inflammation, Eds. J. J. Oppenheim et al. (Elsevier, NY), p.259. As a result, this "activated T cell supernatant" has been used as the source of the various factors. However, because the biological assays for many factors are often time consuming and imprecise, separation of the factors and characterization of their structure and function are formidable tasks. A typical problem has been that a given preparation of T-cell factors often contains several distinct biological activities.
Monoclonal antibody methodology has provided an attractive means to analyze the various components in the activated T cell supernatant. Once monoclonal antibodies are obtained, they can be used to define, to quantitate, and most importantly, to isolate specific molecules in the activated T cell supernatant mixture. This approach has proved very powerful in the analysis of crude antigen mixtures; the most notable example is the studies on surface differentiation antigens and alloantigens of leukocytes. Brodsky, F. M. et al. (1979), Immunol. Rev. 47, 3; Lemke, H. et al. (1979) Immunol. Rev. 47, 175; Kung, P. C. et al. (1979) Science 206, 347; Ledbetter, J. A. and L. A. Herzenberg (1979) Immunol. Rev. 47, 63.
Monoclonal antibodies against two T cell factors of interest have been prepared. Gillis, S. and C. S. Henney (1981), J. Immunol. 126, 1978; Stadler, B. M. et al. (1982), J. Immunol. 128, 1620; Smith, K. et al. (1983), J. Immunol. 131, 1808. In most instances partially purified factors have been used as the immunogens for preparation of hybrid antibody-producing cells and the hybrids have been screened in assays for inhibition of the activity of the various factors. However, the partial purification of individual factors of activated human T-lymphocytes requires a great deal of effort. Further, this approach is useful only for known factors.